Galectin 3 Deficiency Alters Chondrocyte Primary Cilium Formation and Exacerbates Cartilage Destruction via Mitochondrial Apoptosis
Open Access
- 22 February 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (4), 1486
- https://doi.org/10.3390/ijms21041486
Abstract
Mechanical overload and aging are the main risk factors of osteoarthritis (OA). Galectin 3 (GAL3) is important in the formation of primary cilia, organelles that are able to sense mechanical stress. The objectives were to evaluate the role of GAL3 in chondrocyte primary cilium formation and in OA in mice. Chondrocyte primary cilium was detected in vitro by confocal microscopy. OA was induced by aging and partial meniscectomy of wild-type (WT) and Gal3-null 129SvEV mice (Gal3−/−). Primary chondrocytes were isolated from joints of new-born mice. Chondrocyte apoptosis was assessed by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), caspase 3 activity and cytochrome c release. Gene expression was assessed by qRT-PCR. GAL3 was localized at the basal body of the chondrocyte primary cilium. Primary cilia of Gal3−/− chondrocytes were frequently abnormal and misshapen. Deletion of Gal3 triggered premature OA during aging and exacerbated joint instability-induced OA. In both aging and surgery-induced OA cartilage, levels of chondrocyte catabolism and hypertrophy markers and apoptosis were more severe in Gal3−/− than WT samples. In vitro, Gal3 knockout favored chondrocyte apoptosis via the mitochondrial pathway. GAL3 is a key regulator of cartilage homeostasis and chondrocyte primary cilium formation in mice. Gal3 deletion promotes OA development.This publication has 49 references indexed in Scilit:
- Chondrocyte primary cilium is mechanosensitive and responds to low-intensity-ultrasound by altering its length and orientationThe International Journal of Biochemistry & Cell Biology, 2017
- ERK-mediated suppression of cilia in cisplatin-induced tubular cell apoptosis and acute kidney injuryBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2013
- Primary cilia mediate mechanotransduction through control of ATP‐induced Ca2+signaling in compressed chondrocytesThe FASEB Journal, 2011
- Primary cilia regulate mTORC1 activity and cell size through Lkb1Nature, 2010
- Cartilage abnormalities associated with defects of chondrocytic primary cilia in Bardet‐Biedl syndrome mutant miceJournal of Orthopaedic Research, 2009
- Myeloid-related proteins S100A8/S100A9 regulate joint inflammation and cartilage destruction during antigen-induced arthritisAnnals Of The Rheumatic Diseases, 2008
- Loss of Bardet–Biedl syndrome proteins alters the morphology and function of motile cilia in airway epitheliaProceedings of the National Academy of Sciences of the United States of America, 2008
- Gli2 and Gli3 Localize to Cilia and Require the Intraflagellar Transport Protein Polaris for Processing and FunctionPLoS Genetics, 2005
- On the role of galectin-3 in cancer apoptosisApoptosis, 2005
- Embryonic implantation in galectin 1/galectin 3 double mutant miceDevelopmental Dynamics, 1998